N4-(3,4-dichlorophenyl)quinazoline-4,6-diamine | 1290545-26-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N4-(3,4-dichlorophenyl)quinazoline-4,6-diamine
• 英文别名: 3,4-(dichlorophenyl)quinazolin-4,6-diamine；4-N-(3,4-dichlorophenyl)quinazoline-4,6-diamine
• CAS: 1290545-26-4
• 化学式: C₁₄H₁₀Cl₂N₄
• 分子量: 305.166
• InChiKey: YJVNVAOOLFTDHE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-呀啉代)乙基异硫代氰酸酯 、 N4-(3,4-dichlorophenyl)quinazoline-4,6-diamine 以 四氢呋喃 为溶剂， 以79%的产率得到1-(4-((3,4-dichlorophenyl)amino)quinazolin-6-yl)-3-(2-morpholinoethyl)thiourea
  参考文献：
  名称：

  旨在发现突变型EGFR抑制剂；有效的4-芳基氨基-6-脲基和硫脲基-喹唑啉衍生物的设计，合成及体外生物学评价

  摘要：

  设计，合成和评价了具有C-6脲基和硫脲基侧链以及在C-4苯胺基部分具有各种取代基的一系列新的4-苯胺基喹唑啉，并将其评估为野生型（WT）和突变型EGFR抑制剂。大多数化合物抑制EGFR激酶野生型（EGFR WT）的IC 50值都在低纳摩尔范围（<0.495–9.05 nM），并且比参考化合物吉非替尼在表达BaF / 3的EGFR WT中显示出更强的细胞毒性作用。测定了所有合成化合物对吉非替尼不敏感的双突变体表达Del19 / T790M的Ba / F3和表达Ba / F3的L858R / T790M的抗增殖作用。化合物4d，6f，7e表现出显着的抑制作用（IC 50 与拉帕替尼（60.1 nM）相比 ，这些突变株中的Hs2 = 1.76–2.38μM，并且具有显着的Her2酶抑制（IC 50 = 19.2–40.6 nM）。证明了化合物6d，6f，7a，7b和8b的结合模式。此外，测试了对

  DOI：

  10.1016/j.bmc.2016.05.063
• 作为产物：
  描述：

  2-氰基-4-硝基苯胺 在 铁粉 、 溶剂黄146 作用下， 以 乙醇 、 水 为溶剂， 反应 4.5h， 生成 N4-(3,4-dichlorophenyl)quinazoline-4,6-diamine
  参考文献：
  名称：

  Design, synthesis and antitumor evaluation of phenyl N-mustard-quinazoline conjugates

  摘要：

  A series of N-mustard-quinazoline conjugates was synthesized and subjected to antitumor studies. The N-mustard pharmacophore was attached at the C-6 of the 4-anilinoquinazolines via a urea linker. To study the structure-activity relationships of these conjugates, various substituents were introduced to the C-4 anilino moiety. The preliminary antitumor studies revealed that these agents exhibited significant antitumor activity in inhibiting various human tumor cell growths in vitro. Compounds 21b, 21g, and 21h were selected for further antitumor activity evaluation against human breast carcinoma MX-1 and prostate PC-3 xenograft in animal model. These agents showed 54-75% tumor suppression with low toxicity (5-7% body-weight changes). We also demonstrate that the newly synthesized compounds are able to induce DNA cross-linking through alkaline agarose gel shift assay and inhibited cell cycle arrest at G2/M phase. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.01.055

文献信息

• Design, synthesis and antitumor evaluation of phenyl N-mustard-quinazoline conjugates
  作者：Bhavin Marvania、Pei-Chih Lee、Ravi Chaniyara、Huajin Dong、Sharda Suman、Rajesh Kakadiya、Ting-Chao Chou、Te-Chang Lee、Anamik Shah、Tsann-Long Su

  DOI：10.1016/j.bmc.2011.01.055

  日期：2011.3

  A series of N-mustard-quinazoline conjugates was synthesized and subjected to antitumor studies. The N-mustard pharmacophore was attached at the C-6 of the 4-anilinoquinazolines via a urea linker. To study the structure-activity relationships of these conjugates, various substituents were introduced to the C-4 anilino moiety. The preliminary antitumor studies revealed that these agents exhibited significant antitumor activity in inhibiting various human tumor cell growths in vitro. Compounds 21b, 21g, and 21h were selected for further antitumor activity evaluation against human breast carcinoma MX-1 and prostate PC-3 xenograft in animal model. These agents showed 54-75% tumor suppression with low toxicity (5-7% body-weight changes). We also demonstrate that the newly synthesized compounds are able to induce DNA cross-linking through alkaline agarose gel shift assay and inhibited cell cycle arrest at G2/M phase. (C) 2011 Elsevier Ltd. All rights reserved.
• Toward discovery of mutant EGFR inhibitors; Design, synthesis and in vitro biological evaluation of potent 4-arylamino-6-ureido and thioureido-quinazoline derivatives
  作者：Samar Mowafy、A. Galanis、Zainab M. Doctor、Raymond M. Paranal、Deena S. Lasheen、Nahla A. Farag、Pasi A. Jänne、Khaled A.M. Abouzid

  DOI：10.1016/j.bmc.2016.05.063

  日期：2016.8

  evaluated as wild type (WT) and mutant EGFR inhibitors. Most of the compounds inhibited EGFR kinase wild type (EGFR WT) with IC50 values in the low nanomolar range (<0.495–9.05 nM) and displayed more potent cytotoxic effect in BaF/3 expressing EGFR WT than reference compound gefitinib. The anti-proliferative effect of all synthesized compounds against gefitinib insensitive double mutant cell lines Ba/F3

  设计，合成和评价了具有C-6脲基和硫脲基侧链以及在C-4苯胺基部分具有各种取代基的一系列新的4-苯胺基喹唑啉，并将其评估为野生型（WT）和突变型EGFR抑制剂。大多数化合物抑制EGFR激酶野生型（EGFR WT）的IC 50值都在低纳摩尔范围（<0.495–9.05 nM），并且比参考化合物吉非替尼在表达BaF / 3的EGFR WT中显示出更强的细胞毒性作用。测定了所有合成化合物对吉非替尼不敏感的双突变体表达Del19 / T790M的Ba / F3和表达Ba / F3的L858R / T790M的抗增殖作用。化合物4d，6f，7e表现出显着的抑制作用（IC 50 与拉帕替尼（60.1 nM）相比 ，这些突变株中的Hs2 = 1.76–2.38μM，并且具有显着的Her2酶抑制（IC 50 = 19.2–40.6 nM）。证明了化合物6d，6f，7a，7b和8b的结合模式。此外，测试了对